The therapeutic effect of CORM-3 on acute liver failure induced by lipopolysaccharide/D- galactosamine in mice  

作　　者：Bing-Zhu Yan Bao-Shan Yang Hui Li Yan-Fen Zhang Feng-Hua Pei An-Chao Zhu Xiao-Ren Wang Bing-Rong Liu 

机构地区：[1]department of infectious diseases,the second affiliated hospital of harbin medical university,Harbin 150086,China [2]department of gastroenterology and hepatology,the second affiliated hospital of harbin medical university,Harbin 150086,China [3]department of laboratory diagnosis,the second affiliated hospital of harbin medical university,Harbin 150086,China [4]department of histology,the first hospital of harbin city,Harbin 15000l,China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2016年第1期73-80,共8页国际肝胆胰疾病杂志（英文版）

基　　金：supported by a grant from the Science and Technology Research Foundation of Educational Committee,Heilongjiang Province,China(12531294)

摘　　要：BACKGROUND： Acute liver failure （ALF） is a severe and life- threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releas- ing molecule （CORM-3） has been shown to have anti-inflam- matory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism. METHODS： ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM-3 （iCORM-3）. The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activi- ties （ALT and AST） and total bilirubin （TBiL）. Serum levels of inflammatory cytokines （TNF-α, IL-6, IL-1β and IL-10） and liver immunohistochemistry of NF-KB-p65 were determined; the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting. RESULTS： The pretreatment with CORM-3 significantly improved the liver histology and the survival rate of mice compared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines （TNF-α, IL-6 and IL-1β） and increased the anti-in- flammatory cytokine （IL-10） productions in ALF mice. More- over, CORM-3 significantly reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nudear ex- pression of NF-KB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An iCORM-3 failed to prevent acute liver damage induced by LPS/D-GalN. CONCLUSION： These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions.BACKGROUND： Acute liver failure （ALF） is a severe and life- threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releas- ing molecule （CORM-3） has been shown to have anti-inflam- matory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism. METHODS： ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM-3 （iCORM-3）. The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activi- ties （ALT and AST） and total bilirubin （TBiL）. Serum levels of inflammatory cytokines （TNF-α, IL-6, IL-1β and IL-10） and liver immunohistochemistry of NF-KB-p65 were determined; the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting. RESULTS： The pretreatment with CORM-3 significantly improved the liver histology and the survival rate of mice compared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines （TNF-α, IL-6 and IL-1β） and increased the anti-in- flammatory cytokine （IL-10） productions in ALF mice. More- over, CORM-3 significantly reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nudear ex- pression of NF-KB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An iCORM-3 failed to prevent acute liver damage induced by LPS/D-GalN. CONCLUSION： These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions.

关 键 词：acute liver failure CO-releasing molecule-3 CYTOKINES inflammation 

分 类 号：R575.3[医药卫生—消化系统]